Low molecular weight advanced glycation end products predict mortality in asymptomatic patients receiving chronic haemodialysis.

BACKGROUND: Advanced glycation end products (AGEs) have biological properties that may contribute to the premature cardiovascular mortality of haemodialysis patients. This study examines the hypothesis that low molecular weight forms of fluorescent AGEs (LMW fluorescence) predict mortality in haemodialysis patients. METHODS: The LMW fluorescence was measured in 85 patients treated with chronic haemodialysis and prospectively followed for 4 years. The primary outcome of all-cause mortality was assessed using Cox proportional hazards regression model. RESULTS: At the end of the follow-up period 37 (44%) patients died. The median LMW fluorescence level was 24.2 arbitrary units (range: 10.6-148.1 AU) and the receiver operator characteristic (ROC) curve cut-off for mortality was 37.0 AU. The LMW fluorescence predicted death both as a binary variable at the ROC cut-off, and as a continuous log-transformed variable when adjusted for age, albumin and C-reactive protein (CRP). Adjusted for age, albumin and CRP, the hazard ratio for mortality was 3.05 (1.41-6.60, P = 0.005) for LMW fluorescence as a binary variable and 2.71 per log unit (1.37-5.38, P = 0.004) as a continuous log-transformed variable. CONCLUSION: The low molecular weight forms of AGEs predict mortality in patients receiving chronic haemodialysis, and may be important in the mechanisms leading to atherosclerosis and inflammation in such patients.     

黄连不同炮制品中生物碱类成分的比较研究

目的 考察黄连不同炮制品中生物碱成分的差异，为黄连的质量控制和炮制机理的探讨提供参考依据。方法 用高效液相色谱法对黄连不同炮制品中生物碱成分进行分析，比较其色谱图及主要化学成分含量的差异。结果与结论 在不同炮制品中，黄连生物碱的主要组分均得到很好的分离；指纹图谱相似度和主成分含量分析结果表明，黄连的不同炮制品在所测主要成分含量上有一定差异，但各指纹图谱之间的相似度较高。用HPLC法可较全面地反映黄连不同炮制品的生物碱成分，为黄连鉴别和质量控制提供了有效的方法。     

Cross talk in surface electromyograms of human hamstring muscles.

Signals generated from muscles other than the muscle(s) of interest (cross talk) can confound the interpretation of surface electromyograms (EMGs). In this study, the amount of cross talk in surface EMGs of human hamstring muscles was estimated using a protocol in which the quadriceps femoris was electrically stimulated via the femoral nerve. EMGs were recorded from the vastus lateralis and the medial and lateral hamstring muscle groups. The amplitude of the EMG response of the vastus lateralis to electrical stimulation was adjusted to match that of its maximum voluntary effort (MVE) under isometric conditions. Subsequent power density spectrum analysis showed that the median frequencies of the signals generated by electrical stimulation and MVE were not significantly different. In conventional bipolar recordings, cross talk in lateral hamstring EMGs averaged 17.1% MVE and in medial hamstring EMGs 11.3% MVE (average-rectified values). The double differential technique significantly reduced cross talk to 7.6% MVE for the lateral hamstrings, and to 4.2% MVE for the medial hamstrings. The double differential technique appears to be more selective than the bipolar technique when recording EMGs from muscles with highly active neighbors and thus should be used in such situations. Software simulations of the double differential technique also appear to be more selective than the bipolar technique and may be used when the number of amplifiers available is limited.     

The gap between legal rules and practice in advertising non-registered pharmaceutical products : A new method of analysis

The market of non-registered pharmaceutical products is growing fast in number and overall costs, not only in the Netherlands, but also in other European countries. These products often give the impression that the consumer may expect 'an effect as from a drug'. Legally, there is a clear distinction between 'drugs' and 'commodities' in the Netherlands; the question is whether legislation and practice concur. In an investigation we analysed texts of advertisements for non-registered pharmaceutical products published in a popular magazine. A method was developed, based on the legal definition of a drug and jurisprudence, to determine in a qualitative and quantitative way the application of medicinal claims. It transpired that in 65% of the analysed advertisements explicit or implicit claims were made. These products should therefore be subject to drugs legislation. Thus, in the Netherlands there is a gap between legislation and practice in advertising non-registered pharmaceutical products.     

生物制品GMP认证检查的几点体会

本文从生物制品的特点、生物制品对厂房设备的特殊要求、GMP验证和人员素质几个方面。阐述了对生物制品实施GMP认证检查的感想和体会。     

Surface coat of sheep pulmonary intravascular macrophages: Reconstitution,and implication of a glycosyl-phosphatidylinositol anchor

Background: Pulmonary intravascular macrophages (PIMs) of sheep have a globular surface coat that facilitates endocytosis of tracer particles and Escherichia coli lipopolysaccharide, and is disrupted by the heparin and Brefeldin A treatments. The present study investigated the in vivo dynamics of the coat globules following heparin-mediated removal, and the mechanism of globule organization on the plasma membrane of PIMs in vitro. Methods: Sheep were administered heparin at a dose of 50 IU/kg body weight IV, and euthanised at 30 min, 3, 6, 12, 48, and 120 hr (n = 2 for each treatment) after the treatment. Control sheep (n = 2) were injected with normal saline solution. The tissues were processed for an ultrastructural examination and acid phosphatase (ACPase) cytochemistry. Heparintreated lungs were subjected to morphometric analysis of the coat globules. Lung tissues from normal sheep (n = 2) were incubated with phosphatidylinositol-specific-phospholipase C (PIPLC; 2 IU/ml PBS) in vitro for 30 and 75 min. Results: Heparin study: The ultrastructural and morphometric data showed that the coat globules were removed at 30 min and reconstituted within 48 hr of the treatment. The PIMs showed priminent Golgi complexes associated with secretory vesicles, microtubules, and centriole between 3–12 hr of heparin treatment. Acid phosphatase cytochemistry also demonstrated secretory activity in the Golgi complexes of PIMs during the coat reconstitution. PIPLC study: The coat globules of PIMs were removed in a time-dependent mode by the PIPLC treatment without damage to other cell organelles. Conclusions: This study demonstrates a time-dependent reconstitution of the coat of PIMs in conjunction with secretory activity following heparinmediated removal, probably through sequenstration of the globules from blood. This ability is of functional significance as the coat mediates particle endocytosis by the PIMs. The results also suggest the presence of a glycosyl-phosphatidylinositol (GPI) anchor in tethering of globules on the plasma membrane of PIMs to offer a structural basis for their integrity in pulmonary vascular flow. © 1995 Wiley-Liss, Inc.     

Age-Dependent Accumulation of Hybrid Vasopressin-Oxytocin Gene Products but not Hybrid Oxytocin-Vasopressin Products in the Endoplasmic Reticulum of Brattleboro Rats

The age-dependence of the incidence of magnocellular neurosecretory neurons containing abnormal accumulations of peptide in the rough endoplasmic reticulum was examined in homozygous Brattleboro rats and in their wild-type Long Evans counterparts. Neurons in which the immunophenotype of the peptide aggregates indicate that somatic cross-over mutations involving the 5' end of the vasopressin gene and the 3' end of the oxytocin gene have occurred, increased with age in homozygous Brattleboro rats, reaching a maximum of 24 cells per hypothalamus (approximately 0.6% of the vasopressin neurons). The increase occurred in both male and female animals but was significantly greater in females. The average incidence of such cells was 6 times greater in the supraoptic than in the paraventricular nucleus. No such cells could be detected in either nucleus of Long Evans rats despite the evidence for hybrid mRNA in these animals. Moreover, no accumulation of peptide translated from the hybrid mRNAs derived from the 5' end of the oxytocin gene and the 3' end of the vasopressin gene could be detected in either Brattleboro or Long Evans animals. These results strongly suggest that the accumulation of peptide in the rough endoplasmic reticulum of vasopressin neurons in homozygous Brattleboro rats is due to an abnormality other than the somatic crossing-over mutation. A second type of abnormal magnocellular neuron with accumulations of peptide in the rough endoplasmic reticulum, in which the immunophenotype of the peptide reveals products derived only from the oxytocin precursor, was present in both Long Evans and Brattleboro rats, but did not increase with age in Brattleboro rats. The incidence of these cells was similar in the supraoptic and paraventricular nuclei.     

血浆中高级糖化终产物的水平与糖尿病并发症的关系研究

目的 探讨高级糖化终产物与糖尿病并发症的关系。方法 采用本实验室自行研制的竞争性酶联免疫吸附分析方法，测定了糖尿病有并发症组病人血浆95例，糖尿病无并发症组人血浆65例，正常对照65例。结果：在糖尿病有并发症组中，高级糖化终产物（AGEs）浓度[（6．625（1．691）U／mL，n=95]明显高于糖尿病无并发症组[（5．904（2．071）U／mL，n=65，P=0．017]，也明显高于正常人组[（5．337（1．138，n=65，p〈0．005]。以有无并发症为应变量进行多元logistic回归分析显示，血浆AGEs浓度〉6．085U／ml者，糖尿病并发症发生的危险性增加（OR值为2．989，95％可信限为1．407—6．350）。多元逐步线性回归显示：糖尿病病程、冠心病史与血浆AGEs浓度之间有线性关系。结论血浆AGEs浓度是糖尿病发生并发症的独立危险因素。     

电化学人工龋的电化学腐蚀机制研究

目的 研究电化学人工龋的电化学腐蚀机制。方法 采用循环伏安法研究牙片电极在K2SO4溶液中的氧化还原反应；以失重法并结合SPSS统计软件统计分析，评价牙片在KCl和K2SO4介质中恒电位腐蚀情况，并现场监测电解液氢离子浓度的变化情况。结果 在0.0-2.5V电位范围内，牙片电极与石墨电极具有波形类似的循环伏安曲线；在KCl和K2SO4介质中牙片的腐蚀速度无显著差异；2.0V恒电位腐蚀牙片8h后，阳极池本体溶液pH值由7.0平均下降到3.87，阴极池则由7.0平均升高到10.65。结论 在外电场作用下，牙片的阳极腐蚀与介质无关；水的阳极氧化引起阳极区氢离子浓度升高，致使牙齿发生酸溶是电化学人工龋形成的主要决定因素。